Search

Your search keyword '"chromodomain genes"' showing total 3 results
Start Over Descriptor "chromodomain genes"
3 results on '"chromodomain genes"'

1. Rare and de novo coding variants in chromodomain genes in Chiari I malformation.

Author

Sadler, Brooke, Wilborn, Jackson, Antunes, Lilian, Kuensting, Timothy, Hale, Andrew T., Gannon, Stephen R., McCall, Kevin, Cruchaga, Carlos, Harms, Matthew, Voisin, Norine, Reymond, Alexandre, Cappuccio, Gerarda, Burnetti-Pierri, Nicola, Tartaglia, Marco, Niceta, Marcello, Leoni, Chiara, Zampino, Giuseppe, Ashley-Koch, Allison, Urbizu, Aintzane, and Garrett, Melanie E.

Subjects
*ARNOLD-Chiari deformity, *NEUROLOGICAL disorders, *NEURAL development, *GENES, *RHOMBENCEPHALON
Abstract

Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses. A significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes was observed among individuals with CM1 (combined p = 2.4 × 10−10), including 3 de novo loss-of-function variants in CHD8 (LOF enrichment p = 1.9 × 10−10) and a significant burden of rare transmitted variants in CHD3 (p = 1.8 × 10−6). Overall, individuals with CM1 were found to have significantly increased head circumference (p = 2.6 × 10−9), with many harboring CHD rare variants having macrocephaly. Finally, haploinsufficiency for chd8 in zebrafish led to macrocephaly and posterior hindbrain displacement reminiscent of CM1. These results implicate chromodomain genes and excessive brain growth in CM1 pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

2. Rare and de novo coding variants in chromodomain genes in Chiari I malformation

Author

Sadler, B., Wilborn, J., Antunes, L., Kuensting, T., Hale, A. T., Gannon, S. R., Mccall, K., Cruchaga, C., Harms, M., Voisin, N., Reymond, A., Cappuccio, G., Burnetti-Pierri, N., Tartaglia, M., Niceta, M., Leoni, Chiara, Zampino, Giuseppe, Ashley-Koch, A., Urbizu, A., Garrett, M. E., Soldano, K., Macaya, A., Conrad, D., Strahle, J., Dobbs, M. B., Turner, T. N., Shannon, C. N., Brockmeyer, D., Limbrick, D. D., Gurnett, C. A., Haller, G., Leoni C., Zampino G. (ORCID:0000-0003-3865-3253), Sadler, B., Wilborn, J., Antunes, L., Kuensting, T., Hale, A. T., Gannon, S. R., Mccall, K., Cruchaga, C., Harms, M., Voisin, N., Reymond, A., Cappuccio, G., Burnetti-Pierri, N., Tartaglia, M., Niceta, M., Leoni, Chiara, Zampino, Giuseppe, Ashley-Koch, A., Urbizu, A., Garrett, M. E., Soldano, K., Macaya, A., Conrad, D., Strahle, J., Dobbs, M. B., Turner, T. N., Shannon, C. N., Brockmeyer, D., Limbrick, D. D., Gurnett, C. A., Haller, G., Leoni C., and Zampino G. (ORCID:0000-0003-3865-3253)

Abstract

Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses. A significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes was observed among individuals with CM1 (combined p = 2.4 × 10−10), including 3 de novo loss-of-function variants in CHD8 (LOF enrichment p = 1.9 × 10−10) and a significant burden of rare transmitted variants in CHD3 (p = 1.8 × 10−6). Overall, individuals with CM1 were found to have significantly increased head circumference (p = 2.6 × 10−9), with many harboring CHD rare variants having macrocephaly. Finally, haploinsufficiency for chd8 in zebrafish led to macrocephaly and posterior hindbrain displacement reminiscent of CM1. These results implicate chromodomain genes and excessive brain growth in CM1 pathogenesis.

Published
2021

3. Rare and de novo coding variants in chromodomain genes in Chiari I malformation

Author

Karen Soldano, Timothy Kuensting, David D. Limbrick, Brooke Sadler, Melanie E. Garrett, Alfons Macaya, Gabe Haller, Andrew T. Hale, Marco Tartaglia, Jackson Wilborn, Stephen R Gannon, Aintzane Urbizu, Giuseppe Zampino, Donald F. Conrad, Norine Voisin, Tychele N. Turner, Gerarda Cappuccio, Nicola Brunetti-Pierri, Kevin McCall, Douglas L. Brockmeyer, Alexandre Reymond, Matthew B. Harms, Lilian Antunes, Matthew B. Dobbs, Jennifer Strahle, Chevis N. Shannon, Allison E. Ashley-Koch, Carlos Cruchaga, Chiara Leoni, Marcello Niceta, and Christina A. Gurnett

Subjects
Adult, Male, 0301 basic medicine, Proband, de novo mutations, Hindbrain, Haploinsufficiency, Biology, macrocephaly, Polymorphism, Single Nucleotide, Article, Chromodomain, chromodomain genes, 03 medical and health sciences, 0302 clinical medicine, Chiari I malformation, Exome Sequencing, medicine, Genetics, Animals, Humans, Gene, Zebrafish, Genetics (clinical), Foramen magnum, Macrocephaly, rare variants, Brain, Correction, gene burden, medicine.disease, Magnetic Resonance Imaging, Syringomyelia, Human genetics, Arnold-Chiari Malformation, DNA-Binding Proteins, 030104 developmental biology, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Case-Control Studies, zebrafish disease model, Female, Headaches, medicine.symptom, 030217 neurology & neurosurgery
Abstract

Summary Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses. A significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes was observed among individuals with CM1 (combined p = 2.4 × 10−10), including 3 de novo loss-of-function variants in CHD8 (LOF enrichment p = 1.9 × 10−10) and a significant burden of rare transmitted variants in CHD3 (p = 1.8 × 10−6). Overall, individuals with CM1 were found to have significantly increased head circumference (p = 2.6 × 10−9), with many harboring CHD rare variants having macrocephaly. Finally, haploinsufficiency for chd8 in zebrafish led to macrocephaly and posterior hindbrain displacement reminiscent of CM1. These results implicate chromodomain genes and excessive brain growth in CM1 pathogenesis.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results